Cardiac output (pulmonary blood flow) is the rate at which blood is pumped by the heart to the body. Along with the blood pressure, it fundamentally reflects the degree of cardiovascular stability and the adequacy of perfusion of vital organs. Knowledge of the cardiac output will not itself provide a diagnosis of a patient's condition, but can provide information useful in making a diagnosis.
Continuous monitoring of cardiac output is still not performed routinely during anaesthesia and critical care due to the absence of a convenient, safe, non-invasive and accurate and precise method. The established techniques for measuring cardiac output, such as pulmonary thermodilution via a pulmonary artery catheter, are invasive and associated with occasional but serious complications, such as pulmonary artery rupture, and/or are time consuming and heavily operator dependent, as in the case of Doppler echocardiography. Improvements in this field are taking place, such as the development of pulse contour techniques, trans-pulmonary thermodilution, trans-thoracic bio-impedance and derived devices, and methods using pulmonary uptake of inert gases such as nitrous oxide, but these all have limitations, such as poor accuracy under clinical conditions, the need for repeated calibration, invasive central or peripheral cannulation, and/or are simply unsuitable for patients during surgery and critical care who are intubated or ventilated.
Techniques based on the differential Fick principle, such as partial CO2 rebreathing (NICO, Respironics, USA), are among the oldest methods used for cardiac output measurement, and are attractive because of their potentially non-invasive nature. As described in U.S. patent application Ser. No. 12/743,224 and in Peyton P., Continuous Minimally Invasive Peri-operative Monitoring of Cardiac Output by Pulmonary Capnotracking: Comparison with Thermodilution and Transesophageal Echocardiography, J. Clin. Monit. Comput. 2012; 26 (2): 121-32, the inventor has recently developed a technique based on measurement of the rate of gas uptake or elimination of CO2 ({dot over (V)}CO2) by the lungs, referred to herein as the Capnotracking method. The method utilises the differential Fick principle for calibration and an equation relating subsequent changes in {dot over (V)}CO2 and cardiac output ({dot over (Q)}t) to provide an automated, non-invasive, breath-by-breath cardiac output measurement method and system which is suitable for routine use in ventilated patients undergoing general anaesthesia or in intensive care. The accuracy and precision of this technique in patients undergoing major surgery and critical care is similar to that achieved by other available methods across a wide range of haemodynamic states, as described in Peyton P, and Chong S W., Minimally Invasive Measurement of Cardiac Output During Surgery and Critical Care: A Meta-analysis of Accuracy and Precision: Erratum, Anesthesiology, 2012; 116: 972-3 (“Peyton and Chong”).
Methods based on a measured variable such as cardiac output in patients suffer from imperfect accuracy and precision of measurement, the sources of error including systematic bias, and both inter-patient and intra-patient factors. The systematic inaccuracy of methods such as the Capnotracking method arises from physiological or physical factors associated with the underlying principles of the measurement of cardiac output, and of the associated input variables. Inter-patient factors include physiological or physical factors contributing to non-linearity of the method in response to the cardiac output. Intra-patient factors include random variability in the measurement of input variables, and of their association to the cardiac output, and include non-linearity of the method in response to changes in cardiac output, which also contribute to lack of reproducibility of measurement. In general, intra-patient variability is less than inter-patient variability for most methods, resulting in more reliable tracking of changes in cardiac output than their precision in measurement of cardiac output across a wide range of patients and haemodynamic states.
When investigating the precision of a given (“test”) method in measurement of cardiac output in a population of patients, comparison is usually made with an accepted clinical standard, such as bolus thermodilution. The widely quoted criterion for acceptability of precision of a method for measurement of cardiac output, using thermodilution as the reference method, was defined in Critchley L A H, and Critchley J A: A Meta-Analysis of Studies Using Bias and Precision Statistics to Compare Cardiac Output Measurement Techniques, J. Clin. Monit. Comput. 1999; 15: 85-91 (“Critchley and Critchley”). Based on the standard mathematics of error analysis, the error e in agreement between thermodilution and the test method is given by:e=√{square root over (eTd2+et2)}  Equation 1where eTd is the error in measurement of cardiac output by thermodilution, and et is the error in measurement of cardiac output by the test method. Assuming that both thermodilution and the test method have precision in agreement with the true cardiac output (quantitated as the “limits of agreement”, equal to +/−twice the coefficient of variation, within which bounds 95% of measurements are expected to lie as described in Bland J M, Altman D G: Statistical methods for assessing agreement between two methods of clinical measurement, Lancet 1986; i: 307-10 (“Bland and Altman”)) of +/−20%, the precision of agreement of a test method with thermodilution from Equation 1 is +/−28.3%. Approximating this, Critchley and Critchley recommended that +/−30% represents acceptable precision of agreement with thermodilution by a method for measurement of cardiac output.
Comprehensive review of the published literature in the field over a 10 year period has shown that the precision of agreement with thermodilution being achieved by a wide range of currently available methodologies adapted for use in the peri-operative and critical care setting is much wider (i.e., worse) than this. For example, the precision of pulse contour techniques, oesophageal Doppler, trans-thoracic bioimpedance and the partial CO2 rebreathing methods are all between +/−40 to 45% relative to the accompanying thermodilution measurement, as described in Peyton and Chong. The authors could find no evidence from the studies reviewed that this level of precision was improving with time over the 10 year review period. This relatively poor consistency of agreement with the reference method can be in part attributed to a possibly poorer precision of cardiac output measurement by thermodilution than assumed by Critchley and Critchley (see Botero M, Kirby D, Lobato E B, Staples E D, Gravenstein N, Botero M, Kirby D, Lobato E B, Staples E D, Gravenstein N: Measurement of cardiac output before and after cardiopulmonary bypass: Comparison among aortic transit-time ultrasound, thermodilution, and noninvasive partial CO2 rebreathing, J. Cardiothorac. Vasc. Anesth. 2004; 18: 563-72 (“Botero”). Nevertheless, this still represents significantly worse limits of agreement in measurement of the true cardiac output by all techniques than is stipulated as acceptable by these authorities.
In view of the above, there remains a need to find a means for achieving substantially better precision of measurement of cardiac output by techniques adapted for use in peri-operative and critical care patients, so as to prevent misleading data provoking inappropriate clinical decision making, and so as to allow consistent improvements in patient care and clinical outcomes to be obtained from more widespread use of advanced haemodynamic monitoring.
It is desired, therefore, to provide a computerised method and system for monitoring cardiac output of a subject that alleviate one or more difficulties of the prior art, or that at least provide a useful alternative.